Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00704288
First received: June 20, 2008
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to evaluate the objective response rate and 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: XL184
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • To evaluate the objective response rate for subjects with recurrent or progressive glioblastoma multiforme following treatment with XL184 [ Time Frame: Evaluated approx. every 8 weeks ] [ Designated as safety issue: No ]
  • Evaluate safety and tolerability of XL184 [ Time Frame: Assessed at all visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess duration of response, 6-month progression-free survival rate,and overall survival [ Time Frame: Assessed during periodically scheduled visits ] [ Designated as safety issue: No ]
  • Further characterize pharmacokinetics and pharmacodynamic effects of XL184 [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
  • Correlate pathway dysfunction of glioblastoma multiforme-relevant genes such as MET and relevant downstream signaling molecules with clinical outcome [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
  • Correlate changes in serial vascular MRI with clinical outcome and analyze tumor volumetrics based on MRI [ Time Frame: Assessed during periodically scheduled visits, approx. every 8 weeks ] [ Designated as safety issue: No ]
  • Evaluate the glucocorticoid-sparing effect of XL184 [ Time Frame: Assessed periodically ] [ Designated as safety issue: No ]

Enrollment: 222
Study Start Date: May 2008
Study Completion Date: December 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has locally determined histologically confirmed diagnosis of Grade 4 astrocytic tumor.
  • The subject has received prior standard radiation for Grade 3 or 4 astrocytic tumor.
  • The subject has received prior temozolomide therapy for Grade 3 or 4 astrocytic tumor (if in first relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy; if in second relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy either for first-line treatment or for treatment after first relapse).
  • The subject is in first or second Grade 4 relapse, defined as having one or two progressions as Grade 4 astrocytic tumor since the original diagnosis of any grade glioma.
  • The subject must have a baseline brain MRI scan within 14 days prior to first dose of XL184 while either not receiving glucocorticoids during the 5 days prior to the baseline MRI scan or on a stable dose of glucocorticoids during the 5 days prior to the baseline MRI scan.
  • Subjects having undergone recent resection or biopsy of tumor will be eligible as long as all of the following conditions apply: First dose of XL184 occurs at least 28 days after surgery, the subject has recovered from the effects of surgery, and the subject has measurable residual disease.
  • The subject is at least 18 years old.
  • The subject has a KPS (Karnofsky Performance Scale) of ≥ 70%.
  • The subject is capable of understanding the protocol and has signed the informed consent document.
  • The subject has adequate organ and marrow function.
  • Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study drug.
  • Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

  • The subject has received non-standard radiation therapy for glioblastoma, non-anti-angiogenic therapy (including investigational agents, small-molecule kinase inhibitors, and biologic agents) or non-cytotoxic hormonal agent within 28 days of the first scheduled dose of XL184 or mitomycin C within 42 days of the first scheduled dose of XL184, other investigational therapy (including agents not specified above) within 28 days of the first scheduled dose of XL184, or prior treatment with nitrosoureas (including carmustine wafer) at any time.
  • Some subjects may not have had any prior VEGF- or VEGFR2-based anti-angiogenic therapy (such as bevacizumab, cediranib, or pazopanib).
  • Some subjects may not have had bevacizumab within 14 days of the first scheduled dose of XL184.
  • The subject is receiving warfarin (or other coumarin derivatives) at study entry and unable to switch to low molecular weight heparin.
  • The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
  • The subject is unable to undergo MRI scan (eg, has pacemaker).
  • The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before the first dose of XL184 (eg, carbamazepine, phenytoin, phenobarbital, primidone).
  • The subject has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from adverse events (AEs) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered before study enrollment.
  • The subject has evidence of wound dehiscence.
  • The subject is pregnant or breast-feeding.
  • The subject has serious intercurrent illness, such as uncontrolled hypertension, unhealed wounds from recent surgery or cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within the past 3 months, myocardial infarction within the past 6 months, or active infection requiring systemic treatment/hospitalization within 2 weeks of the first scheduled dose of XL184
  • The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
  • The subject has received any live virus vaccine within 28 days or any inactivated vaccine within 7 days prior to first dose of XL184.
  • The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed ≥ 2 years previously) or currently has evidence of malignancy (unless non-melanoma skin cancer or in situ carcinoma of the cervix).
  • The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulations.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704288

Locations
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, North Carolina
Duke University, The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, United States, 27710
United States, Texas
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Exelixis
  More Information

No publications provided

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00704288     History of Changes
Other Study ID Numbers: XL184-201
Study First Received: June 20, 2008
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
GBM
Malignant gliomas

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 22, 2014